Although the association between an occurrence of intussusception and rotavirus replication in the gut has not been established, the only licensed rotavirus vaccine (RotaShield) which is a live attenuated vaccine delivered orally has been withdrawn from market because of its putative association with intussusception. Since it is difficult to solve this problem experimentally, we decided to seek an alternative approach to the development of a safe and effective rotavirus vaccine employing a non-viable or temperature sensitive (ts) rotavirus vaccine which is administered intranasally and thus bypassing virus replication in the gut. As a first step of the project, we studied pathogenicity and immunogenicity of a live candidate rotavirus vaccine by using a homologous system of rhesus monkeys and live rhesus monkey rotavirus (RRV). Two juvenile rhesus monkeys were infected intranasally with approximately 106 PFU of RRV. The animals did not show any adverse clinical signs. One animal shed RRV in stools for 7 days and developed a seroresponse 3 weeks later. Nasal swabs collected from this animal during the first 3 days post-challenge contained low levels (8 x 101 to 5 x 102 PFU/ml) of RRV. The second animal shed RRV in stools during the first two days post-challenge and did not develop a seroresponse. Low levels (~ 1 x 101 PFU/ml) of RRV were detected in nasal swabs obtained from this animal during the first two days post-challenge. Levels of serum IgA antibodies in animals are being examined.